Hochdurchsatz-Analyse pathogener Eigenschaften Herpesvirus-8-kodierter Gene in Endothelzellen

内皮细胞中疱疹病毒 8 编码基因致病特性的高通量分析

• 批准号: 5389059
• 负责人: Professor Dr. Michael Stürzl
• 金额: --
• 依托单位: Abteilung Molekulare und Experimentelle Chirurgie (AMEC)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5389059?language=en
• 关键词: Hochdurchsatz; Analyse; pathogener; Eigenschaften; Herpesvirus

Kaposi's sarcoma (KS) is an angioproliferative disease. Human herpesvirus-8 (HHV-8) has an etiologic role in KS. It is unknown, as yet, which genes of HHV-8 may trigger KS development. In this project we will systematically determine the effects of each of the 84 genes encoded by HHV-8 in primary human endothelial cell cultures. Particularly tumor relevant functions, affecting cell proliferation, adhesiveness for monocytes, migration and apoptosis will be investigated. In addition, the effect of each gene will be tested in combination with every other HHV-8 gene and with the proto-oncogenes c-myc and ras. Finally, the whole approach will be performed with endothelial cells that have been subjected to different external stimulations by inflammatory cytokines, angiogenic growth factors and the HIV-1-Tat protein. To this goal, reverse transfection of arrayed expression plasmids will be established as a high throughput transfection system which allows to determine the functions of hundreds of genes in parallel. This study will identify the genes of HHV-8 with the highest tumorigenic activation potential in endothelial cells. Moreover, our approach may provide a useful platform technology to determine the vasculopathogenic function of any set of viral and cellular genes in the scope of the Schwerpunktprogramm.

卡波西肉瘤是一种血管增生性疾病。人类疱疹病毒-8（HHV-8）在KS中具有病因学作用。目前尚不清楚HHV-8的哪些基因可能触发KS的发展。在这个项目中，我们将系统地确定由HHV-8编码的84个基因中的每一个在原代人内皮细胞培养中的作用。特别是肿瘤相关的功能，影响细胞增殖，单核细胞的粘附，迁移和凋亡将被研究。此外，每种基因的作用将与每种其他HHV-8基因以及原癌基因c-myc和ras联合检测。最后，整个方法将用内皮细胞进行，所述内皮细胞已经受到炎性细胞因子、血管生成生长因子和HIV-1-达特蛋白的不同外部刺激。为此，阵列表达质粒的反向转染将被建立为允许平行测定数百个基因的功能的高通量转染系统。本研究将确定HHV-8在内皮细胞中具有最高致瘤激活潜力的基因。此外，我们的方法可以提供一个有用的平台技术，以确定在Schwerpunktprogramm的范围内的任何一组病毒和细胞基因的血管致病功能。